tbuckley/cabot-search huggingface dataset:
Local and systemic immune profiles of human pancreatic ductal adenocarcinoma revealed by single-cell mass cytometry
Authors: Thomas P Brouwer, Natasja L de Vries, Tamim Abdelaal, Ricki T Krog, Zheng Li, Dina Ruano, Arantza Fariña, Boudewijn P F Lelieveldt, Hans Morreau, Bert A Bonsing, Alexander L Vahrmeijer, Frits Koning, Noel F C C de Miranda
Journal: Journal for ImmunoTherapy of Cancer (2022)

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy in need of effective (immuno)therapeutic treatment strategies. For the optimal application and development of cancer immunotherapies, a comprehensive understanding of local and systemic immune profiles in patients with PDAC is required. Here, our goal was to decipher the interplay between local and systemic immune profiles in treatment-naïve patients with PDAC.The immune composition of PDAC, matched non-malignant pancreatic tissue, regional lymph nodes, spleen, portal vein blood, and peripheral blood samples (collected before and after surgery) from 11 patients with PDAC was assessed by measuring 41 immune cell markers by single-cell mass cytometry. Furthermore, the activation potential of tumor-infiltrating lymphocytes as determined by their ability to produce cytokines was investigated by flow cytometry. In addition, the spatial localization of tumor-infiltrating innate lymphocytes in the tumor microenvironment was confirmed by multispectral immunofluorescence.We found that CD103+CD8+ T cells with cytotoxic potential are infrequent in the PDAC immune microenvironment and lack the expression of activation markers and checkpoint blockade molecule programmed cell death protein-1 (PD-1). In contrast, PDAC tissues showed a remarkable increased relative frequency of B cells and regulatory T cells as compared with non-malignant pancreatic tissues. Besides, a previously unappreciated innate lymphocyte cell (ILC) population (CD127-CD103+CD39+CD45RO+ ILC1-like) was discovered in PDAC tissues. Strikingly, the increased relative frequency of B cells and regulatory T cells in pancreatic cancer samples was reflected in matched portal vein blood samples but not in peripheral blood, suggesting a regional enrichment of immune cells that infiltrate the PDAC microenvironment. After surgery, decreased frequencies of myeloid dendritic cells were found in peripheral blood.Our work demonstrates an immunosuppressive landscape in PDAC tissues, generally deprived of cytotoxic T cells and enriched in regulatory T cells and B cells. The antitumor potential of ILC1-like cells in PDAC may be exploited in a therapeutic setting. Importantly, immune profiles detected in blood isolated from the portal vein reflected the immune cell composition of the PDAC microenvironment, suggesting that this anatomical location could be a source of tumor-associated immune cell subsets.
Mavacamten: First Approval
Authors: Susan J. Keam
Journal: Drugs (2022)

Mavacamten (Camzyos™) is an oral small-molecule cardiac myosin inhibitor developed by MyoKardia, Inc., a wholly owned subsidiary of Bristol Myers Squibb, for the treatment of hypertrophic cardiomyopathy (HCM) and diseases of diastolic dysfunction. In April 2022, mavacamten was approved for use in the USA in the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive HCM to improve functional capacity and symptoms. This article summarizes the milestones in the development of mavacamten leading to this first approval for the treatment of adults with symptomatic NYHA class II-III obstructive HCM.
Methodological and reporting issues for meta‐analysis of immune checkpoint inhibitor‐associated cardiotoxicity. Letter regarding the article ‘Cardiotoxicity associated with immune checkpoint inhibitor therapy: a meta‐analysis’. Reply
Authors: Nestor Rubio‐Infante, Yoel A. Ramírez‐Flores, Elena C. Castillo, Omar Lozano, Gerardo García‐Rivas, Guillermo Torre‐Amione
Journal: European Journal of Heart Failure (2022)
The Charcot Foot Reflects a Response to Injury That Is Critically Distorted by Preexisting Nerve Damage: An Imperfect Storm
Authors: William Jeffcoate, Fran Game
Journal: Diabetes Care (2022)

It has been recognized since comprehensive descriptions by Jean-Martin Charcot in 1868 and 1883 that development of what is usually known as neuropathic osteoarthropathy (or the Charcot foot) requires the coincidence of neuropathy and inflammation. Despite this, detailed understanding of the causes has remained remarkably limited in the succeeding century and a half. The aim of this descriptive account is to draw particular attention to the processes involved in both the onset and resolution of the inflammation that is an essential component of active disease. The principal observation is that while neuropathy is common in people with diabetes, the inflammation and secondary skeletal damage that characterize neuropathic osteoarthropathy are observed in only a small minority of people with diabetes and with neuropathy. We therefore argue that the key to understanding the causes of the Charcot foot is to focus equally on those who have active disease as well as those who do not. Although neuropathy is essential for development of the disorder, neuropathy also has an adverse impact on the mechanisms involved in the onset of inflammation, and these may be critically affected in the majority of those who are susceptible. The Charcot foot is uncommon in people with diabetes (or any other cause of neuropathy) because the large majority of those with neuropathy may have also lost the capacity to mount the specific inflammatory reaction that is essential for its development.
Long-term Survival After Sleeve Gastrectomy Versus Gastric Bypass in a Binational Cohort Study
Authors: Dag Holmberg, Giola Santoni, Joonas H. Kauppila, Sheraz R. Markar, Jesper Lagergren
Journal: Diabetes Care (2022)

OBJECTIVE Bariatric surgery prolongs life expectancy in severely obese individuals, but it is uncertain which of the two dominating bariatric procedures, sleeve gastrectomy or gastric bypass, offers the best long-term survival. RESEARCH DESIGN AND METHODS This was a population-based cohort study of primary laparoscopic sleeve gastrectomy compared with gastric bypass for obesity in Sweden and Finland between 1 January 2007 and 31 December 2020. The risk of all-cause mortality was calculated using multivariable Cox regression, providing hazard ratios (HRs) with 95% CIs adjusted for age, sex, hypertension, diabetes, Charlson comorbidity index, country, and calendar year. RESULTS Among 61,503 patients (median age 42 years; 75.4% women), who contributed 415,712 person-years at risk (mean 6.8 person-years), 1,571 (2.6%) died during follow-up. Compared with patients who underwent gastric bypass (n = 51,891 [84.4%]), the sleeve gastrectomy group (n = 9,612 [15.6%]) had similar all-cause mortality during the entire study period (HR 0.98, 95% CI 0.81–1.20), but decreased all-cause mortality in more recent years (HR 0.72, 95% CI 0.54–0.97, from 2014 onward). Diabetes interacted statistically significantly with the type of bariatric surgery, with higher all-cause mortality after sleeve gastrectomy than after gastric bypass (HR 1.54, 95% CI 1.06–2.24). CONCLUSIONS The overall survival following sleeve gastrectomy seems to compare well with gastric bypass and may even be better during recent years. A tailored surgical approach in relation to patients’ diabetes status may optimize survival in patients selected for bariatric surgery (i.e., sleeve gastrectomy for patients without diabetes and gastric bypass for patients with diabetes).
Optimal Number of Steps per Day to Prevent All-Cause Mortality in People With Prediabetes and Diabetes
Authors: Jesus del Pozo-Cruz, Francisco Alvarez-Barbosa, Daniel Gallardo-Gomez, Borja del Pozo Cruz
Journal: Diabetes Care (2022)

We aimed to examine the dose-response associations between the number of steps per day and all-cause mortality among adults with prediabetes and diabetes.This prospective study used data from 1,194 U.S. adults with prediabetes and 493 with diabetes for whom accelerometer-derived steps per day could be retrieved. Mortality was ascertained through the National Death Index (February 25, 2019). Splines were used to assess the dose-response associations between steps per day and all-cause mortality.Over ∼9 years of follow-up, 200 adults with prediabetes and 138 with diabetes died. Nonlinear associations akin to an L shape were observed. We estimated an optimal dose of ∼10,000 steps per day to reduce the risk of all-cause mortality for both individuals with prediabetes and those with diabetes.Accumulating more steps per day up to ∼10,000 steps per day may lower the risk of all-cause mortality of adults with prediabetes and diabetes.
How do we know who may replace each other in triadic conflict roles?
Authors: Lotte Thomsen
Journal: Behavioral and Brain Sciences (2022)

Group representations need not reduce to triadic conflict roles, although we infer group membership from them. A conceptual primitive of <group> as one solidary, bounded unity or clique may motivate and facilitate reasoning about cooperative group interactions in context with and without intergroup conflict and may also be necessary for representing which agents would replace one another in a triadic conflict.
A 3D Bioprinted In Vitro Model of Pulmonary Artery Atresia to Evaluate Endothelial Cell Response to Microenvironment
Authors: Martin L. Tomov, Lilanni Perez, Liqun Ning, Huang Chen, Bowen Jing, Andrew Mingee, Sahar Ibrahim, Andrea S. Theus, Gabriella Kabboul, Katherine Do, Sai Raviteja Bhamidipati, Jordan Fischbach, Kevin McCoy, Byron A. Zambrano, Jianyi Zhang, Reza Avazmohammadi, Athanasios Mantalaris, Brooks D. Lindsey, David Frakes, Lakshmi Prasad Dasi, Vahid Serpooshan, Holly Bauser‐Heaton
Journal: Advanced Healthcare Materials (2022)

Adv. Healthcare Mater. 2021, 10, 2100968 https://doi.org/10.1002/adhm.202100968 In the original version of this article, the last sentence of the Acknowledgements is missing a funding source. The correct sentence at the end of the Acknowledgement should read: This research was also funded in part by R00HL138288 and K12HD072245 from the National Institutes of Health and funding from the "Saving Tiny Hearts Society".
Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN
Authors: Hartmut Döhner, Andrew H. Wei, Frederick R. Appelbaum, Charles Craddock, Courtney D. DiNardo, Hervé Dombret, Benjamin L. Ebert, Pierre Fenaux, Lucy A. Godley, Robert P. Hasserjian, Richard A. Larson, Ross L. Levine, Yasushi Miyazaki, Dietger Niederwieser, Gert Ossenkoppele, Christoph Röllig, Jorge Sierra, Eytan M. Stein, Martin S. Tallman, Hwei-Fang Tien, Jianxiang Wang, Agnieszka Wierzbowska, Bob Löwenberg
Journal: Blood (2022)

Abstract The 2010 and 2017 editions of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults are widely recognized among physicians and investigators. There have been major advances in our understanding of AML, including new knowledge about the molecular pathogenesis of AML, leading to an update of the disease classification, technological progress in genomic diagnostics and assessment of measurable residual disease, and the successful development of new therapeutic agents, such as FLT3, IDH1, IDH2, and BCL2 inhibitors. These advances have prompted this update that includes a revised ELN genetic risk classification, revised response criteria, and treatment recommendations.
Laparoscopic versus open distal pancreatectomy with or without splenectomy: A propensity score analysis in Japan
Authors: Takaaki Konishi, Takeshi Takamoto, Michimasa Fujiogi, Yohei Hashimoto, Hiroki Matsui, Kiyohide Fushimi, Masahiko Tanabe, Yasuyuki Seto, Hideo Yasunaga
Journal: International Journal of Surgery (2022)
Author's correction for Euro Surveill. 2022;27(25)
Journal: Eurosurveillance (2022)

© This work is licensed under a Creative Commons Attribution 4.0 International License. Closure This is a corrected article applying to the following content: One Health surveillance of West Nile and Usutu viruses: a repeated cross-sectional study exploring seroprevalence and endemicity in Southern France, 2016 to 2020
G-CSF plus azacitidine versus azacitidine alone for patients with high-risk myelodysplastic syndrome: academic, open label, randomized trial
Authors: Tomáš Stopka, Lubomír Minařík, Nina Dusilková, Michal Pešta, Vojtěch Kulvait, Martin Špaček, Zuzana Zemanová, Marta Kalousová, Anna Jonášová
Journal: Blood Cancer Journal (2022)

GA trial is registered under EudraCT#: 2013-001639-38.
Treatment of hepatocellular carcinoma in sub-Saharan Africa: challenges and solutions
Authors: Eduard Jonas, Marc Bernon, Barbara Robertson, Chris Kassianides, Elie Keli, Kwaku Offei Asare, Isaac Olusegun Alatise, Michael Okello, Nana Oumarou Blondel, Kenedy Ondede Mulehane, Zeki Abdurahman Abubeker, Alaaeldin Awad Nogoud, Pueya Rashid Nashidengo, Onesai Chihaka, Christian Tzeuton, Geoffrey Dusheiko, Mark Sonderup, C Wendy Spearman
Journal: The Lancet. Gastroenterology & hepatology (2022)
RATTLE: reference-free reconstruction and quantification of transcriptomes from Nanopore sequencing
Authors: Ivan de la Rubia, Akanksha Srivastava, Wenjing Xue, Joel A. Indi, Silvia Carbonell-Sala, Julien Lagarde, M. Mar Albà, Eduardo Eyras
Journal: Genome biology (2022)

Abstract Nanopore sequencing enables the efficient and unbiased measurement of transcriptomes. Current methods for transcript identification and quantification rely on mapping reads to a reference genome, which precludes the study of species with a partial or missing reference or the identification of disease-specific transcripts not readily identifiable from a reference. We present RATTLE, a tool to perform reference-free reconstruction and quantification of transcripts using only Nanopore reads. Using simulated data and experimental data from isoform spike-ins, human tissues, and cell lines, we show that RATTLE accurately determines transcript sequences and their abundances, and shows good scalability with the number of transcripts.
Thrombectomy alone versus intravenous alteplase plus thrombectomy in patients with stroke: an open-label, blinded-outcome, randomised non-inferiority trial
Authors: Urs Fischer, Johannes Kaesmacher, Daniel Strbian, Omer Eker, Christoph Cognard, Patricia S Plattner, Lukas Bütikofer, Pasquale Mordasini, Sandro Deppeler, Vitor M Pereira, Jean François Albucher, Jean Darcourt, Romain Bourcier, Guillon Benoit, Chrysanthi Papagiannaki, Ozlem Ozkul-Wermester, Gerli Sibolt, Marjaana Tiainen, Benjamin Gory, Sébastien Richard, Jan Liman, Marielle Sophie Ernst, Marion Boulanger, Charlotte Barbier, Laura Mechtouff, Liqun Zhang, Gaultier Marnat, Igor Sibon, Omid Nikoubashman, Arno Reich, Arturo Consoli, Bertrand Lapergue, Marc Ribo, Alejandro Tomasello, Suzana Saleme, Francisco Macian, Solène Moulin, Paolo Pagano, Guillaume Saliou, Emmanuel Carrera, Kevin Janot, María Hernández-Pérez, Raoul Pop, Lucie Della Schiava, Andreas R Luft, Michel Piotin, Jean Christophe Gentric, Aleksandra Pikula, Waltraud Pfeilschifter, Marcel Arnold, Adnan H Siddiqui, Michael T Froehler, Anthony J Furlan, René Chapot, Martin Wiesmann, Paolo Machi, Hans-Christoph Diener, Zsolt Kulcsar, Leo H Bonati, Claudio L Bassetti, Mikael Mazighi, David S Liebeskind, Jeffrey L Saver, Jan Gralla, Angelika Alonso, Caroline Arquizan, Xavier Barreau, Rémy Beaujeux, Daniel Behme, Tobias Boeckh-Behrens, Christian Boehme, Martí Boix, Grégoire Boulouis, Nicolas Bricout, Nicolas Broc, Carlo W. Cereda, Emmanuel Chabert, Tae-Hee Cho, Alessandro Cianfoni, Vincent Costalat, Christian Denier, Frederico Di Maria, Richard du Mesnil de Rochemont, Patricia Fearon, Anna Ferrier, Sebastian Fischer, Maxime Gauberti, Marie Gaudron, Laetitia Gimenez, Christoph Globas, Michael Görtler, Mayank Goyal, Ruediger Hilker-Roggendorf, Michael D. Hill, Vi Tuan Hua, Lisa Humbertjean, Olav Jansen, Simon Jung, Georg Kägi, Michael E. Kelly, Ilka Kleffner, Michael Knoflach, Krassen Nedeltchev, Lars Udo Krause, Kimmo Lappalainen, Margaux Lefebvre, Joe Leyon, Liang Liao, Jean-Sebastien Liegey, Christian Loehr, Patrik Michel, Stefania Nannoni, Patrick Nicholson, Lorena Nico, Michael Obadia, Julien Ognard, Ayokunle Ogungbemi, Jean-Marc Olivot, Simon Escalard, Marco Pasi, Lissa Peeling, Jane Perez, Martina Petersen, Eike Piechowiak, Roberto Raposo, Silja Räty, Sarah C. Reitz, Sebastià Remollo, Luca Remonda, Ian Rennie, Manuel Requena, Alexander Riabikin, Roberto Riva, Aymeric Rouchaud, Andrea Rosi, Marta Rubiera, Laurent Spelle, Marlena Schnieder, Joanna D. Schaafsma, Tilman Schubert, Jörg B. Schulz, Mohammed Siddiqui, Sébastien Soize, Michael Sonnberger, Emmanuel Touze, Aude Triquenot, Guillaume Turc, Lucy Vieira, Wagih Ben Hassen, Judith N. Wagner, Katrin Wasser, Johannes Weber, Holger Wenz, David Weisenburger-Lile, Fritz Wodarg, Valérie Wolff, Silke Wunderlich
Journal: The Lancet (2022)
Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study
Authors: Junfang Yang, Jiaping He, Xian Zhang, Jingjing Li, Zhenguang Wang, Yongliang Zhang, Liyuan Qiu, Qionglu Wu, Zhe Sun, Xun Ye, Wenjie Yin, Wei Cao, Lianjun Shen, Martina Sersch, Peihua Lu
Journal: Blood Cancer Journal (2022)

Abstract To improve clinical outcomes and shorten the vein-to-vein time of chimeric antigen receptor T (CAR-T) cells, we developed the FasT CAR-T (F-CAR-T) next-day manufacturing platform. We report the preclinical and first-in-human clinical studies evaluating the safety, feasibility, and preliminary efficacy of CD19 F-CAR-T in B-cell acute lymphoblastic leukemia (B-ALL). CD19 F-CAR-T cells demonstrated excellent proliferation with a younger cellular phenotype, less exhaustion, and more effective tumor elimination compared to conventional CAR-T cells in the preclinical study. In our phase I study (NCT03825718), F-CAR-T cells were successfully manufactured and infused in all of the 25 enrolled pediatric and adult patients with B-ALL. CD19 F-CAR-T safety profile was manageable with 24% grade 3 cytokine release syndrome (CRS) and 28% grade 3/4 neurotoxicity occurring predominantly in pediatric patients. On day 14, 23/25 patients achieved minimal residual disease (MRD)-negative complete remission (CR), and 20 subsequently underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) within 3 months post F-CAR-T therapy. Fifteen of 20 patients were disease-free with a median remission duration of 734 days. One patient relapsed and 4/20 died from transplant-related mortality. Of the three patients who did not undergo allo-HSCT, two remained in CR until 10 months post-F-CAR-T. Our data indicate that anti-CD19 FasT CAR-T shows promising early efficacy for B-ALL. Further evaluations in larger clinical studies are needed.
Continuous Microfiber Wire Mandrel‐Less Biofabrication for Soft Tissue Engineering Applications (Adv. Healthcare Mater. 13/2022)
Authors: Arianna Adamo, Joseph G. Bartolacci, Drake D. Pedersen, Marco G. Traina, Seungil Kim, Antonio Pantano, Giulio Ghersi, Simon C. Watkins, William R. Wagner, Stephen F. Badylak, Antonio D'Amore
Journal: Advanced Healthcare Materials (2022)
Medicines associated with dependence or withdrawal symptoms: summary of NICE guideline
Authors: Serena Carville, Margaret Lally, Catherine Stannard, Louise Trewern
Journal: BMJ (2022)

<h3>Introduction</h3> Induced abortion is legal in Italy but with restrictions. The online abortion provider Women on Web (WoW) serves as an alternative way to access abortion. The COVID-19 pandemic has affected sexual and reproductive health worldwide. Italy was one of the first countries hit by the pandemic and imposed strict lockdown measures. We aimed to understand why women requested WoW abortion in Italy and how this was affected by the pandemic. <h3>Methods</h3> We conducted an observational study analysing requests made to WoW before and during the pandemic. We analysed 778 requests for medical abortion from Italy between 1 March 2019 to 30 November 2020 and compared the characteristics of requests submitted before and during the pandemic. We also performed subgroup analysis on teenagers and COVID-19-specific requests. <h3>Results</h3> There was an increase in requests during the COVID-19 pandemic compared with the previous year (12% in the first 9 months). The most common reasons for requesting a telemedicine abortion through WoW were privacy-related (40.9%); however, this shifted to COVID-19-specific (50.3%) reasons during the pandemic. Requests from teenagers (n=61) were more frequently made at later gestational stages (p=0.003), had a higher prevalence of rape (p=0.003) as the cause of unwanted pregnancies, and exhibited less access to healthcare services compared with adult women. <h3>Conclusions</h3> There was an increase in total demand for self-managed abortion during the pandemic and reasons for requesting an abortion changed, shifting from privacy-related to COVID-19-specific reasons. This study also highlighted the uniquely vulnerable situation of teenagers with unwanted pregnancies seeking self-managed abortion.
Retinoic Acid Receptor Activation Reduces Metastatic Prostate Cancer Bone Lesions by Blocking the Endothelial-to-Osteoblast Transition
Authors: Guoyu Yu, Paul G. Corn, Pengfei Shen, Jian H. Song, Yu-Chen Lee, Song-Chang Lin, Jing Pan, Sandeep K. Agarwal, Theocharis Panaretakis, Maurizio Pacifici, Christopher J. Logothetis, Li-Yuan Yu-Lee, Sue-Hwa Lin
Journal: Cancer Research (2022)

Abstract Metastatic prostate cancer in the bone induces bone-forming lesions that contribute to progression and therapy resistance. Prostate cancer–induced bone formation originates from endothelial cells (EC) that have undergone endothelial-to-osteoblast (EC-to-OSB) transition in response to tumor-secreted BMP4. Current strategies targeting prostate cancer–induced bone formation are lacking. Here, we show that activation of retinoic acid receptor (RAR) inhibits EC-to-OSB transition and reduces prostate cancer–induced bone formation. Treatment with palovarotene, an RARγ agonist being tested for heterotopic ossification in fibrodysplasia ossificans progressiva, inhibited EC-to-OSB transition and osteoblast mineralization in vitro and decreased tumor-induced bone formation and tumor growth in several osteogenic prostate cancer models, and similar effects were observed with the pan-RAR agonist all-trans-retinoic acid (ATRA). Knockdown of RARα, β, or γ isoforms in ECs blocked BMP4-induced EC-to-OSB transition and osteoblast mineralization, indicating a role for all three isoforms in prostate cancer–induced bone formation. Furthermore, treatment with palovarotene or ATRA reduced plasma Tenascin C, a factor secreted from EC-OSB cells, which may be used to monitor treatment response. Mechanistically, BMP4-activated pSmad1 formed a complex with RAR in the nucleus of ECs to activate EC-to-OSB transition. RAR activation by palovarotene or ATRA caused pSmad1 degradation by recruiting the E3-ubiquitin ligase Smad ubiquitination regulatory factor1 (Smurf1) to the nuclear pSmad1/RARγ complex, thus blocking EC-to-OSB transition. Collectively, these findings suggest that palovarotene can be repurposed to target prostate cancer–induced bone formation to improve clinical outcomes for patients with bone metastasis. Significance: This study provides mechanistic insights into how RAR agonists suppress prostate cancer–induced bone formation and offers a rationale for developing RAR agonists for prostate cancer bone metastasis therapy. See related commentary by Bhowmick and Bhowmick, p. 2975
Paranoia reveals the complexity in assigning individuals to groups on the basis of inferred intentions
Authors: Anna Greenburgh, Nichola Raihani
Journal: Behavioral and Brain Sciences (2022)

Abstract We suggest that variation, error, and bias will be essential to include in a complete computational theory of groups – particularly given that formation of group representations must often rely on inferences of intentions. We draw on the case study of paranoia to illustrate that intentions that do not correspond to group-constitutive roles may often be perceived as such.